Long-term inhibition of Rho kinase suppresses intimal thickening in autologous vein grafts in rabbits. 2006

Tadashi Furuyama, and Kimihiro Komori, and Hiroaki Shimokawa, and Yasuharu Matsumoto, and Toyokazu Uwatoku, and Katsuya Hirano, and Yoshihiko Maehara
Department of Surgery and Science, Kyushu University, Graduate School of Medical Sciences, Fukuoka, Japan. tfuru@surg2.med.kyushu-u.ac.jp

BACKGROUND Rho kinase plays an important role in vascular smooth muscle cell (VSMC) contraction and other cellular functions, such as proliferation, migration, and apoptosis. Recent studies have demonstrated that long-term inhibition of Rho kinase suppresses coronary artery spasm and vascular lesion formation after arterial injury. In the cardiovascular surgery field, intimal thickening in vein grafts is the major cause of late graft failure, for which no effective treatment has yet been developed. In this study, we examined whether long-term inhibition of Rho kinase suppresses intimal thickening in autologous vein grafts in rabbits. METHODS Male rabbits were randomly divided into two groups and received normal chow (control group) or a special chow containing 0.09% fasudil (fasudil group). After oral administration, fasudil is metabolized to a specific Rho kinase inhibitor, hydroxyfasudil. Each group underwent reversed autologous vein graft surgery with the internal jugular vein into the left common carotid artery. At 1, 2, and 4 weeks after the operation, we examined the extent of intimal thickening of the graft and VSMC proliferation and apoptosis. RESULTS The intimal thickening was significantly suppressed in the fasudil group compared with the control group at 2 and 4 weeks after the operation. In the fasudil group, VSMC proliferation was suppressed at 1 and 2 weeks after the operation, whereas VSMC apoptosis was enhanced at 2 weeks after the procedure. CONCLUSIONS These results indicate that Rho kinase is substantially involved in the pathogenesis of intimal thickening of vein grafts and that it is an important therapeutic target for the prevention of graft failure.

UI MeSH Term Description Entries
D007124 Immunoenzyme Techniques Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens. Antibody Enzyme Technique, Unlabeled,Enzyme Immunoassay,Enzyme-Labeled Antibody Technique,Immunoassay, Enzyme,Immunoperoxidase Techniques,Peroxidase-Antiperoxidase Complex Technique,Peroxidase-Labeled Antibody Technique,Antibody Enzyme Technic, Unlabeled,Enzyme-Labeled Antibody Technic,Immunoenzyme Technics,Immunoperoxidase Technics,Peroxidase-Antiperoxidase Complex Technic,Peroxidase-Labeled Antibody Technic,Antibody Technic, Enzyme-Labeled,Antibody Technic, Peroxidase-Labeled,Antibody Technics, Enzyme-Labeled,Antibody Technics, Peroxidase-Labeled,Antibody Technique, Enzyme-Labeled,Antibody Technique, Peroxidase-Labeled,Antibody Techniques, Enzyme-Labeled,Antibody Techniques, Peroxidase-Labeled,Enzyme Immunoassays,Enzyme Labeled Antibody Technic,Enzyme Labeled Antibody Technique,Enzyme-Labeled Antibody Technics,Enzyme-Labeled Antibody Techniques,Immunoassays, Enzyme,Immunoenzyme Technic,Immunoenzyme Technique,Immunoperoxidase Technic,Immunoperoxidase Technique,Peroxidase Antiperoxidase Complex Technic,Peroxidase Antiperoxidase Complex Technique,Peroxidase Labeled Antibody Technic,Peroxidase Labeled Antibody Technique,Peroxidase-Antiperoxidase Complex Technics,Peroxidase-Antiperoxidase Complex Techniques,Peroxidase-Labeled Antibody Technics,Peroxidase-Labeled Antibody Techniques,Technic, Enzyme-Labeled Antibody,Technic, Immunoenzyme,Technic, Immunoperoxidase,Technic, Peroxidase-Antiperoxidase Complex,Technic, Peroxidase-Labeled Antibody,Technics, Enzyme-Labeled Antibody,Technics, Immunoenzyme,Technics, Immunoperoxidase,Technics, Peroxidase-Antiperoxidase Complex,Technics, Peroxidase-Labeled Antibody,Technique, Enzyme-Labeled Antibody,Technique, Immunoenzyme,Technique, Immunoperoxidase,Technique, Peroxidase-Antiperoxidase Complex,Technique, Peroxidase-Labeled Antibody,Techniques, Enzyme-Labeled Antibody,Techniques, Immunoenzyme,Techniques, Immunoperoxidase,Techniques, Peroxidase-Antiperoxidase Complex,Techniques, Peroxidase-Labeled Antibody
D007601 Jugular Veins Veins in the neck which drain the brain, face, and neck into the brachiocephalic or subclavian veins. Jugular Vein,Vein, Jugular,Veins, Jugular
D008297 Male Males
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D011897 Random Allocation A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. Randomization,Allocation, Random
D000704 Analysis of Variance A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable. ANOVA,Analysis, Variance,Variance Analysis,Analyses, Variance,Variance Analyses
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017346 Protein Serine-Threonine Kinases A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors. Protein-Serine-Threonine Kinases,Serine-Threonine Protein Kinase,Serine-Threonine Protein Kinases,Protein-Serine Kinase,Protein-Serine-Threonine Kinase,Protein-Threonine Kinase,Serine Kinase,Serine-Threonine Kinase,Serine-Threonine Kinases,Threonine Kinase,Kinase, Protein-Serine,Kinase, Protein-Serine-Threonine,Kinase, Protein-Threonine,Kinase, Serine-Threonine,Kinases, Protein Serine-Threonine,Kinases, Protein-Serine-Threonine,Kinases, Serine-Threonine,Protein Kinase, Serine-Threonine,Protein Kinases, Serine-Threonine,Protein Serine Kinase,Protein Serine Threonine Kinase,Protein Serine Threonine Kinases,Protein Threonine Kinase,Serine Threonine Kinase,Serine Threonine Kinases,Serine Threonine Protein Kinase,Serine Threonine Protein Kinases
D017536 Carotid Artery, Common The two principal arteries supplying the structures of the head and neck. They ascend in the neck, one on each side, and at the level of the upper border of the thyroid cartilage, each divides into two branches, the external (CAROTID ARTERY, EXTERNAL) and internal (CAROTID ARTERY, INTERNAL) carotid arteries. Common Carotid Artery,Arteries, Common Carotid,Artery, Common Carotid,Carotid Arteries, Common,Common Carotid Arteries
D017539 Tunica Intima The innermost layer of an artery or vein, made up of one layer of endothelial cells and supported by an internal elastic lamina. Internal Elastic Lamella,Internal Elastic Lamina,Tunica Intima Vasorum,Vascular Intima,Arterial Intima,Venous Intima,Arterial Intimas,Elastic Lamella, Internal,Elastic Lamina, Internal,Internal Elastic Laminas,Intima, Arterial,Intima, Vascular,Intima, Venous,Lamella, Internal Elastic,Lamina, Internal Elastic,Vascular Intimas,Venous Intimas

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